Systems and methods for trans-esophageal sympathetic ganglion recruitment

ABSTRACT

A method may include positioning a catheter, including at least one electrode, within an esophagus such that the electrode is proximate to at least one sympathetic ganglion. The methods may further include recruiting the sympathetic ganglion via an electrical signal, monitoring the recruitment of the sympathetic ganglion, and, based on the monitoring the recruitment of the sympathetic ganglion, adjusting the electrical signal from the at least one electrode.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims priority to U.S. Provisional Application No.62/541,652, filed on Aug. 4, 2017, the entire disclosure of which ishereby incorporated by reference in its entirety.

In general, all publications, patent applications, and patents mentionedin this specification are herein incorporated by reference in theirentirety to the same extent as if each individual document wasspecifically individually indicated to be incorporated by reference.

TECHNICAL FIELD

The embodiments of this disclosure generally relate to methods, systems,and devices for the diagnosis, mitigation, and treatment of neuralinjury (e.g., aneurism, stroke, concussion, etc.). In some examples, thepresent disclosure is directed to a method of reducing the occurrence ofbrain cell damage or death of a patient. One exemplary aspect isdirected to a method of reducing the occurrence of brain cell damage ordeath caused by a transient cerebral hypoxia/ischemia condition, a braininflammation condition, or a traumatic brain injury (TBI) event. Anotherexemplary aspect is directed to devices, systems, and methods forreducing brain and/or cognitive injury in patients diagnosed with asubarachnoid hemorrhage (SAH).

BACKGROUND

SAH is characterized by bleeding into the space between the arachnoidmembrane and the pia mater of the brain. SAH may occur as a result of ahead injury or as a consequence of a cerebral aneurysm. The worldwideincidence of SAH has been estimated to be 7-25 per 100,000 person-years;from 1% to 7% of cerebrovascular accidents (CVAs, e.g., strokes) are theresult of SAH. In some instances, SAH may result in delayed cerebralischemia associated with a cerebral vasospasm (CVS). Studies haveestimated 33% to 46% of patients with SAH will experience a clinicallyrelevant CVS. Further, the delayed cerebral ischemia resulting from anSAH-related CVS may significantly impair a patient's functionality andquality of life, with only 20% of patients leaving the hospital withtheir pre-CVA neurological status.

Without being limited by theory, it is believed the combination ofintracerebral hemorrhage and raised intracranial pressure may lead to anover-activation of the sympathetic system leading to an increased riskof CVS. This over-activation is thought to occur through two mechanisms,a direct effect on the medulla that leads to activation of thedescending sympathetic nervous system and a local release ofinflammatory mediators that circulate to the peripheral circulationwhere they activate the sympathetic system. The over-activation of thesympathetic system may result in a release of adrenaline, a suddenincrease in blood pressure, increased contractility of the ventriclesystem, increased vasoconstriction, and/or increased systemic vascularresistance. Over-activation of the sympathetic system can result incardiac arrhythmias, electrocardiographic changes, and/or cardiac arrestthat may occur rapidly after the onset of hemorrhage. In some cases, aneurogenic pulmonary edema may develop which is characterized byincreased pressure within the pulmonary circulation, leading to leakingof fluid from the pulmonary capillaries into the air spaces of the lung.

To limit the negative consequences resulting from SAH, physicians haveexperimented with sympathetic ganglion blocks in an attempt to preventan over-activation of the sympathetic system. For example, an anestheticmay be delivered to the sympathetic ganglia via hypodermic needle usingultrasound visualization, fluoroscopy, or computed tomography (CT)scanning. In one procedure, a needle is inserted between the trachea andcarotid sheath. In another procedure, a needle is inserted rostral tothe sternoclavicular junction. Such invasive techniques involving theinsertion of a needle into the neck and/or near the trachea areassociated with the development of pneumothorax. Further, thesetechniques require large, immobile, and/or expensive imaging equipmentand procedures, such as, for example, ultrasound visualization,fluoroscopy, or CT scanning.

Such procedures require specialized training, large-scale equipmentand/or imagery machinery, and may only be performed in few hospitalswith specialized staff. Further, such approaches are limited in theregions of cervical sympathetic ganglia that may be blocked due to theinvasive nature of such procedures, the proximity of nerves,vasculature, and trachea, and the imprecision of anesthetic blocks.Additionally, the feasibility of using such techniques as a preventivemeasure is uncertain. The local anesthetics used in such blocks may lastonly several hours, while the increased risk of a delayed CVS may lastup to 14 days after the SAH. Further, the long-term consequences ofcontinued use of such anesthetics as nerve blocking agents are not yetknown and are potentially severe.

SUMMARY

Embodiments of the present disclosure relate to, among other things,systems, devices, and methods for treating, including preventing andmoderating, brain injury. Each of the embodiments disclosed herein mayinclude one or more of the features described in connection with any ofthe other disclosed embodiments.

This disclosure includes methods of treatment. In some aspects, themethods may include positioning a catheter within the esophagus, thecatheter including at least one electrode, wherein the catheter ispositioned so that the at least one electrode is proximate to at leastone sympathetic ganglion. The methods may further include recruiting thesympathetic ganglion via an electrical signal from the at least oneelectrode. This may include recruiting at least one of a left stellateganglion or a right stellate ganglion via the electrical signal from theat least one electrode. The recruiting of the sympathetic ganglion mayinclude blocking the transmission of nerve signals along the sympatheticganglion.

In some examples, the methods may further include where at least oneelectrode includes a plurality of electrodes. A first electrode of theplurality of electrodes may be positioned on a surface opposite a secondelectrode of the plurality of electrodes, where the first electrode andsecond electrode are positioned at the same axial level. In someaspects, an electrical signal may be transmitted by the plurality ofelectrodes to recruit the left stellate ganglion and the right stellateganglion. In some examples, at least one electrode is positionedinferior to the C4 vertebra and superior to the T2 vertebra. In someaspects, a method may include positioning a catheter including at leastfour electrodes. The catheter may be positioned through an oroesophagealor a nasoesophageal cavity.

In some examples of methods, the electrical signal is pulsed and has afrequency of 100 Hz to 100 kHz and an amplitude of 10 μA to 20 mA. Themethods may further include monitoring the recruitment of thesympathetic ganglia. The monitoring may include observing palpebraldroop, performing an electroencephalogram, measuring pupil diameter,observing a color change in a sclera, measuring a skin temperature,measuring a skin perspiration, performing a transcranial Dopplerultrasonogram, or a combination thereof. In some aspects, based on themonitoring the recruitment of the sympathetic ganglia, the methods mayfurther comprise adjusting the electrical signal from at least oneelectrode.

In further aspects, systems for treatment may include an esophagealcatheter, one or more sensors for sensing a physiologic parameterindicative of a state of the sympathetic ganglia, and a controller incommunication with the at least one electrode and the one or moresensors, where, upon receiving a first signal from the one or moresensors based on the sensed physiological parameter, the controllerinduces the at least one electrode to transmit an electrical signal thatrecruit the sympathetic ganglia. In some examples, the esophagealcatheter comprises at least one electrode configured to be positionedwithin the esophagus proximate to at least one sympathetic ganglion. Theone or more sensors may measure or monitor pupil dilation, skintemperature, skin perspiration, blood flow, electroencephalography, or acombination thereof. In other aspects, upon receiving a second signalfrom the one or more sensors, the controller induces the at least oneelectrode to cease transmitting the electrical signal or the controllerinduces the at least one electrode to adjust one or more of theamplitude or frequency of the transmitted electrical signal.

In some examples, the at least one electrode of the systems include aplurality of electrodes configured to independently transmit electricalsignals and a first electrode of the plurality of electrodes isconfigured to be positioned proximate to a left stellate ganglion and asecond electrode of the plurality of electrodes is configured to bepositioned proximate to a right stellate ganglion. In some aspects, uponreceiving a second signal from one or more sensors, the controller mayinduce one of the plurality of electrodes to adjust one or more of theamplitude or frequency of the electrical signal.

In further examples, an esophageal catheter may include a intermediatesection operable to radially expand from a contracted state to anexpanded state, a plurality of electrodes, and/or a feeding tube. Atleast two of the plurality of electrodes are farther displaced when theintermediate section is in an expanded state. The intermediate sectionmay include an inflatable member. In some embodiments, the intermediatesection may comprise at least two arms. The at least two arms may beconnected by a tether and each arm may include a joined end, a proximalend, and at least one electrode positioned between the joined and theproximal end. The joined end may connect to the joined end of one ormore other arms and the proximal end may be farther displaced from theproximal end of one or more other arms when the intermediate section isin an expanded state as compared to when the intermediate section is ina contracted state.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate non-limiting embodiments of thepresent disclosure and together with the description serve to explainthe principles of the disclosure.

FIG. 1A illustrates the anatomy of selected tissues and anatomicallumens in a person's head and neck, along with an exemplary esophagealcatheter placed within the esophagus, according to one or moreembodiments of the present disclosure;

FIG. 1B illustrates the anatomy of selected tissues, anatomical lumens,and organs in a person's head, neck, and torso, along with an exemplaryesophageal catheter placed within the esophagus, according to one ormore embodiments of the present disclosure;

FIG. 2A illustrates an axial cross section including the anatomy ofselected nerves, lumens, and bones in a person's neck, according to oneor more embodiments of the present disclosure;

FIG. 2B illustrates the axial cross section shown in FIG. 2A, along withexemplary esophageal catheter electrodes placed within the esophagus;

FIG. 3A illustrates a perspective view of an esophageal catheter,according to one or more embodiments of the present disclosure;

FIG. 3B illustrates a cross-sectional view depicting the esophagealcatheter shown in FIG. 3A, along line 3B-3B of FIG. 3A;

FIG. 4A illustrates a perspective view of an esophageal catheter in acontracted state, according to one or more embodiments of the presentdisclosure;

FIG. 4B illustrates a cross-sectional view depicting the esophagealcatheter in a contracted state shown in FIG. 4A, along line 4B-4B ofFIG. 4A;

FIG. 4C illustrates a perspective view of the esophageal catheter ofFIG. 4A in an expanded state;

FIG. 4D illustrates a cross-sectional view depicting the esophagealcatheter in an expanded state, along line 4D-4D of FIG. 4C;

FIG. 5A illustrates a perspective view of an esophageal catheter in acontracted state, according to one or more embodiments of the presentdisclosure;

FIG. 5B illustrates a perspective view of the esophageal catheter shownin FIG. 5A, in an expanded state;

FIG. 5C illustrates a cross-sectional view depicting the esophagealcatheter in an expanded state shown in FIG. 5B, along line 5C-5C of FIG.5B;

FIG. 6 illustrates a schematic view of a system having an esophagealcatheter, a control unit, and one or more sensors, according variousembodiments of the present disclosure; and

FIG. 7 is a flowchart of a method according to an embodiment of thepresent disclosure.

DETAILED DESCRIPTION

Throughout the following description, specific details are set forth toprovide a more thorough understanding to persons skilled in the art. Thefollowing description of examples of the technology is not intended tobe exhaustive or to limit the system to the precise forms of any exampleembodiment. Accordingly, the description and drawings are to be regardedin an illustrative sense, rather than a restrictive sense.

Further aspects of the disclosures and features of example embodimentsare illustrated in the appended drawings and/or described in the text ofthis specification and/or described in the accompanying claims. It maybe understood that both the foregoing general description and thefollowing detailed description are exemplary and explanatory only andare not restrictive of the invention, as claimed. As used herein, theterms “comprises,” “comprising,” “including,” “having,” or othervariations thereof, are intended to cover a non-exclusive inclusion suchthat a process, method, article, or apparatus that comprises a list ofelements does not include only those elements, but may include otherelements not expressly listed or inherent to such a process, method,article, or apparatus. Additionally, the term “exemplary” is used hereinin the sense of “example,” rather than “ideal.” As used herein, theterms “about,” “substantially,” and “approximately,” indicate a range ofvalues within +/−15% of a stated value.

Reference will now be made in detail to examples of the presentdisclosure described above and illustrated in the accompanying drawings.Wherever possible, the same reference numbers will be used throughoutthe drawings to refer to the same or like parts.

The terms “proximal” and “distal” are used herein to refer to therelative positions of the components of an exemplary medical device orinsertion device. When used herein, “proximal” refers to a positionrelatively closer to the exterior of the body or closer to an operatorusing the medical device or insertion device. In contrast, “distal”refers to a position relatively further away from the operator using themedical device or insertion device, or closer to the interior of thebody.

One or more embodiments may relate to a device and/or method to delivertransesophageal neuromodulation to a cervical or thoracic sympatheticganglion (e.g., a stellate ganglion) in order to increase brainperfusion. Given the proximity of the esophagus to target cervicalsympathetic ganglia, an esophageal catheter including electrodes may bedeployed within the esophagus to delivery high-frequency (e.g., greaterthan or equal to 1 kHz) electrical signals (e.g., electrical pulsetrains).

In general, embodiments of this disclosure relate to systems, medicaldevices, and methods for recruiting sympathetic ganglia and preventing,modulating, controlling, or treating injury (e.g., injury of the brain).For example, the injury may be caused or enhanced by a TBI event. Asused herein, the term “injury” may refer to an alteration in cellular ormolecular integrity, activity, level, robustness, state, or otheralteration that is traceable to an event. For example, brain injury maybe neuronal injury resulting from stress (repetitive stress),inflammation, oxidative stress, disease, pain, stroke, and/or physicalinjury such as surgery or trauma (e.g., a TBI event). An SAH or aresulting CVS may exacerbate, worsen, or cause a brain injury. One ormore methods herein may relate to treating and monitoring patients withan SAH to prevent or reduce incidence of a delayed CVS. Further, one ormore methods herein may be applied to improve outcomes in patients withan acute stroke or a traumatic brain injury. Recruitment of at least onesympathetic ganglion may control, reduce or mitigate inflammation fromischemia or traumatic brain injury that may cause secondary injury toneurons.

In one or more embodiments, recruiting a nerve may include blocking thetransmission of nerve signals along one or more cells (e.g. neurons).Recruiting a nerve may include transmitting an electrical signal (e.g.,a recruitment signal) to the nerve that interferes with the transmissionof a normal nerve signal. In some aspects, recruiting a nerve may be anongoing process via the transmission of a repeating, pulsed, electricalsignal to the nerve. The repeating, pulsed, electrical signal may stopaxonal conduction of nerve signals. In instances, a nerve receiving anongoing recruitment signal may be considered recruited. In someembodiments, a nerve which is unable to conduct nerve signals may beconsidered recruited. Ceasing the recruitment of a nerve may be referredto herein as releasing the nerve. Similarly, a nerve that is no longerrecruited, but was once recruited, may be referred to as released.

In one or more embodiments, a method of treatment comprises positioninga catheter including at least one electrode within an esophagus suchthat the at least one electrode is proximate to at least one sympatheticganglion, and recruiting the at least one sympathetic ganglion via anelectrical signal from the at least one electrode. At least oneelectrode may be positioned inferior to the C4 vertebrae and superior tothe T2 vertebrae and/or along the dorsal wall of the esophagus. In someembodiments at least one electrode may be positioned inferior to the C5vertebrae and superior to the T1 vertebrae. Alternatively or inaddition, at least one electrode is positioned 20 centimeters (cm) to 27cm from the edge of the nasogastric cavity. Further, recruiting at leastone sympathetic ganglia may include recruiting one or more of the leftstellate ganglion or the right stellate ganglion. In some embodiments,recruiting at least one sympathetic ganglia may including blocking thetransmission of nerve signals along the sympathetic ganglia, such as,for example, along the left stellate ganglion or along the rightstellate ganglion. In some embodiments, recruitment of the left stellateganglion may be used in patients presenting with cardiac indicationsand/or upper left limb pain. In other embodiments, recruitment of theright stellate ganglion may be used in patients with cardiacarrhythmias. The recruitment of both the left stellate ganglion and theright stellate ganglion may be used to treat patients presenting withcardiac arrhythmias such as, for example, ventricular arrhythmia.

The methods may further include monitoring, sensing, and/or testing oneor more functions, activity, or other parameters of the brain or nervoussystem, obtaining the results of the sensing or tests, and analyzingthese results, for example, to determine the effect of the transmittedelectrical signal on nervous function and/or activity. Based on the testresults and their analysis, parameters (e.g., timing, duration, profile,and/or intensity) for the electrical signal may be generated ormodified, and one or more nerves may be recruited or released based onthe parameters. In some cases, the methods may include testing nervousfunction and the status of one or more nerve recruitments. Exemplarytests on the status of nerve (e.g., sympathetic ganglia) recruitmentsinclude detection of electrodermal activity, monitoring heart ratevariability, evaluating responses related to the control of pupildiameter and blood flow to the eye, measuring peripheral blood flow(e.g., via transcranial Doppler ultrasonogram), heart rate and bloodpressure variability analysis, thermoregulatory sweat test, magneticresonance imaging (MRI, e.g., functional MRI), single-photon emissioncomputed tomography (SPECT), evaluation of electroencephalography (EEG)waveforms, the measurement of visual, audio and somatosensory evokedpotentials, changes in absolute vital sign values, and changes in painthreshold. The tests may also include detecting chemistry (e.g., levelsand activities of proteins or other molecules such as inflammation- orpain-related molecules) in the blood or other bodily fluids. Thechemistry tests may include measuring the level and/concentrations ofTNF-α, other cytokines, serotonin, gastrin, norepinephrine, and/or otherhormones. For example, methods of the present disclosure may includemonitoring the recruitment of the sympathetic ganglia by observingpalpebral droop, performing an electroencephalogram, measuring pupildiameter, observing a color change in the sclera, measuring skintemperature, performing a transcranial Doppler ultrasonogram, or acombination thereof.

The tests of nerve recruitment may be performed prior to, during, orafter an electrical signal is transmitted or at different stages ofrecruitment signal transmission. For example, the tests may be performedbefore, during, or after a transmitted electrical signal (e.g., before,during, or after one or more periods of a pulsed electrical signal).Alternatively or in addition, the tests may be performed before, during,or after recruitment of a nerve. Brain function and/or sympatheticganglia recruitment status or activity may be determined based on thetest results. The results from the tests performed at different timesmay be compared to each other or to reference threshold values orranges, e.g. thresholds or ranges that indicate normal nervous functionor other levels of nervous function. In such cases, brain functionand/or sympathetic ganglia recruitment status may be determined based onthe comparisons.

For a patient receiving or having received treatment via an electricalsignal from an esophageal catheter, the brain function and/orsympathetic ganglia recruitment status in the patient may be detectedand compared to parameters indicative of normal function and/or statusof the brain and/or the nerves. If a difference or a significantdifference is determined, one or more parameters of the electricalsignal transmitted by at least one electrode may be modified to adjustthe recruitment of the sympathetic ganglia. The adjustment may beperformed continuously (e.g., based on real-time monitoring of brainfunction and/or sympathetic ganglion recruitment status) for deliveringoptimal and personalized therapy to the patient.

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring the palpebral droop or slumpof a patient. When transmission of nerve signals through the sympatheticganglia is blocked (e.g., when the sympathetic ganglia is recruited) oneor more superior eyelids of a patient may droop, slump or distendfurther from its normal open position. In some instances, blocking thetransmission of nerve signals through the left stellate ganglion maycause the left superior eyelid to droop. Additionally or in thealternative, blocking the transmission of nerve signals through theright stellate ganglion may cause the right superior eyelid to droop.Monitoring the palpebral droop of a patient (e.g., observing whethereither or both superior eyelids are drooping) may inform a controllerand/or a user (e.g., physician or patient) of the recruitment status ofone or more nerves, such as, for example, the sympathetic ganglia (e.g.,left stellate ganglion and/or right stellate ganglion). As describedherein, when a physiological parameter (e.g., palpebral droop) isobserved and/or monitored, the observation may be made by one or moresensors and/or a user (e.g., patient, physician, nurse, or otherhealthcare professional). The one or more sensors and/or users maytransmit the observation to a controller, in some embodiments.

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring the brain activity of apatient via an electroencephalogram (EEG). Generally, an EEG records theelectrical activity of a brain via electrodes placed along the surfaceof a scalp or transcutaneously through the scalp. Through theelectrodes, an EEG records voltage fluctuations resulting from thecurrent within neurons of the brain. After the transmission of nervesignals through a sympathetic ganglion has been blocked (e.g., when thesympathetic ganglion is recruited) for 5 minutes to 45 minutes (e.g., 5minutes, 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 40minutes), decreases in spectral edge frequency (SEF), beta to thetaratio (BTR), median frequency (MF), and beta to delta ratio (BDR) may bedetected via EEG. The general operation of an EEG and how to detectdecreases in SEF, BTR, MF, and/or BDR is known to those skilled in theart and, for the sake of brevity, will not be described in furtherdetail herein. Monitoring the EEG of a patient (e.g., observingdecreases in SEF, BTR, MF, and/or BDR) may inform a controller and/or auser (e.g., physician or patient) of the recruitment status of one ormore nerves, such as, for example, the sympathetic ganglia (e.g., leftstellate ganglion and/or right stellate ganglion). In some embodiments,a decrease of at least approximately 60%, at least approximately 65%, atleast approximately 70%, at least approximately 75%, or at leastapproximately 80% in SEF, BTR, MF, and/or BDR may indicate recruitmentof the sympathetic ganglia. In some embodiments, at least a 10% decreasein the bispectral index (BIS) of a patient, as monitored via EEF, mayindicate recruitment of at least one sympathetic ganglion. In otherembodiments, at least a 15% decrease or a 10-20% decrease in BIS mayindicate recruitment of at least one sympathetic ganglion.

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring the pupil diameter and/orsclera color of a patient. When transmission of nerve signals throughthe sympathetic ganglia is blocked (e.g., when a sympathetic ganglion isrecruited) a pupils of a patient may decrease in diameter. Further, theblocking of the transmission of nerve signals through the sympatheticganglia (e.g., recruitment of the sympathetic ganglia) may cause one ormore sclera of a patient to redden (i.e., change color from white to redor pink). Pupil contraction and sclera reddening may both be the resultof increased blood flow to the eye as a result of the sympatheticganglia recruitment. In some instances, blocking the transmission ofnerve signals through the left stellate ganglion may cause the leftpupil to contract (e.g., decrease in diameter) and/or the left sclera toredden. Additionally or in the alternative, blocking the transmission ofnerve signals through the right stellate ganglion may cause the rightpupil to contract (e.g., decrease in diameter) and/or the right sclerato redden. Monitoring the pupil size and/or sclera color of a patientmay inform a controller and/or a user (e.g., physician or patient) ofthe recruitment status of one or more nerves, such as, for example, thesympathetic ganglia (e.g., left stellate ganglion and/or right stellateganglion). In some embodiments, a difference of greater than or equal to0.2 mm (e.g., greater than or equal to 0.3 mm or greater than or equalto 0.4 mm) in pupil diameter may indicate recruitment of at least onesympathetic ganglion. In other words, the measurement of one pupil of apatient as having a diameter 0.2 mm greater than the other pupil mayindicate sympathetic ganglia recruitment.

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring one or more skintemperatures of a patient. After transmission of nerve signals throughthe sympathetic ganglia has been blocked (e.g., when a sympatheticganglion is recruited) for 2 minutes to 30 minutes (e.g., 3 minutes, 5minutes, 8 minutes, 10 minutes, 13 minutes, 15 minutes, 18 minutes, 20minutes, 25 minutes, 30 minutes) the skin temperature on a limb and faceof a patient may increase by 0.25° C. to 2° C. (e.g., 0.5° C. to 1.5°C.). In a healthy patient with normal nervous system function, limb andface temperature is a few degrees Celsius (e.g., 1-5° C.) below corebody temperature. When the transmission of nerve signals through asympathetic ganglion is blocked (e.g., the sympathetic ganglion isrecruited), the skin temperature and face temperature of a patient mayincrease as blood flow increases to the head and limbs. Monitoring theskin temperature of the limbs and/or face of a patient (e.g., observingwhether either or both skin temperatures increases) may inform acontroller and/or a user (e.g., physician or patient) of the recruitmentstatus of one or more nerves, such as, for example, the sympatheticganglia (e.g., left stellate ganglion and/or right stellate ganglion).

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring the skin perspiration of apatient. Monitoring the skin perspiration may include monitoring eitherthe rate of sweat or the density of sweat from or on one or more areasof skin. In at least one embodiment, skin perspiration is measured onboth limbs of a patient. If either side of the patient has at least a40% decrease (e.g., at least a 50% decrease or at least a 60% decrease)in skin perspiration rate or skin perspiration density compared to theother side, the sympathetic ganglia may be recruited.

In one or more embodiments, monitoring the recruitment of a nerve (e.g.sympathetic ganglia) may include monitoring blood circulation in thebrain of a patient via a transcranial Doppler ultrasonogram. Generally,a transcranial Doppler ultrasonogram measures the velocity of blood flowthrough a brain's blood vessels by measuring the echoes of ultrasoundwaves passing from the blood vessels through the cranium. Like othertypes of Doppler ultrasonography, data or images can be generated basedon measuring the Doppler effect of ultrasound waves introduced to thepatient, influenced relative to the velocity of a fluid traveling withinan anatomical space. After the transmission of nerve signals through astellate ganglion has been blocked, the velocity of blood circulation inthe brain may increase, which can be detected by a transcranial Dopplerultrasonogram. The general operation of a Doppler ultrasonogram is knownto those skilled in the art and will not be described in further detailfor sake of brevity. Monitoring the transcranial Doppler ultrasonogramof a patient (e.g., observing an increase in blood circulation velocityin the brain) may inform a controller and/or a user (e.g., physician orpatient) of the recruitment status of one or more nerves, such as, forexample, the sympathetic ganglia (e.g., left stellate ganglion and/orright stellate ganglion). For example, in some embodiments, a decreasein the blood flow in the middle cerebral artery by at leastapproximately 10% (e.g., at least approximately 15%) may be indicativeof recruitment of the sympathetic ganglia. In other embodiments, anincrease of at least approximately 15% (e.g., at least approximately 18%or at least approximately 20%) in cerebral perfusion pressure may beevidence of sympathetic ganglia recruitment. Further, a decrease of atleast 7.5% (e.g., a decrease of at least 10% or a decrease of at least15%) in zero flow pressure may indicate recruitment of the sympatheticganglia.

Any of the previously described examples of monitoring recruitment of anerve may be used alone or in combination with any other example ofmonitoring recruitment of a nerve. This monitoring may includemonitoring the recruitment of the sympathetic ganglia (e.g., leftstellate ganglion and/or right stellate ganglion). Further, in someembodiments, the methods of the present disclosure may include, based onthe monitoring the recruitment of the sympathetic ganglia, adjusting theelectrical signal from at least one electrode.

In one or more embodiments described herein, a system may includemedical devices for performing the methods described in the disclosure.The system, as described below, may include components such as acatheter having a tubular member and one or more electrode assemblies, asignal generator to provide stimulation energy to the electrodeassemblies, one or more sensors to sense the condition of the patient,and one or more control components allowing another device (includingone or more hardware components and/or software components) or user(e.g., a physician, nurse, other healthcare provider, or a patient) toadjust the parameters of the transmitted electrical signal. Thedifferent embodiments of the various system components may be combinedand used together in any logical arrangement. Furthermore, individualfeatures or elements of any described embodiment may be combined with orused in connection with the individual features or elements of otherembodiments. The various embodiments may further be used in differentcontexts than those specifically described herein. For example, thedisclosed electrode structures may be combined or used in combinationwith various deployment systems known in the art for various diagnosticand/or therapeutic applications.

The systems and methods described in this disclosure may help to achieveat least one or more of the following to a patient: preventing,modulating, controlling, or treating brain injury. In some embodiments,the systems and methods herein may reduce brain injury via recruitmentof the sympathetic ganglia. One or more electrical signals may be usedto recruit one or more nerves and interfere with aberrant pain signalsand help mitigate cell death. Electrical signals (e.g., pulsedelectrical signals) transmitted via electrodes placed proximate to thesympathetic ganglia (e.g., in the esophagus near the left stellateganglion or the right stellate ganglion) to recruit the sympatheticganglia and temporarily block afferent signals. The transmittedelectrical signal (e.g. the recruitment signal) may have a frequency of100 hertz (Hz) to 100 kHz, including, for example, a frequency of 1 kHzto 50 kHz or 1 kHz to 30 kHz. Further, the recruitment signal may havean amplitude of 10 micro-amperes (μA) to 20 mA per phase. Otherfrequencies and amplitudes which may block conduction of axonal nervesignals without causing electrode corrosion or tissue damage are alsocontemplated.

Based on the monitoring of the recruitment of a sympathetic ganglion,the recruitment signal may be adjusted. For example, in one or moreembodiments, a patient may be monitored for one or more indications of asympathetic ganglion recruitment (e.g., recruitment of the left stellateganglion and/or recruitment of the right stellate ganglion) as describedabove, via one or more sensors of the system. In response to a signalfrom one or more sensors that the sympathetic ganglion is recruited, therecruitment signal may be altered or ceased. For example, the frequencyof the recruitment signal might be increased or decreased. Similarly,the amplitude of the recruitment signal might be increased or decreased.In response to a signal that the stellate ganglion is recruited, therecruitment signal might be reduced to a lover level or cease beingtransmitted. In other embodiments, a recruitment signal might betemporarily stopped if the system receives a signal that the stellateganglion is recruited. Similarly, in response to a signal from one ormore sensors that the sympathetic ganglion is not recruited, therecruitment signal may be altered. For example, the frequency and/oramplitude of the recruitment signal might be increased or decreased.

One or more components of systems described herein may include aplurality of electrodes (e.g., an esophageal catheter comprising aplurality of electrodes). The plurality of electrodes may be similarlyshaped or have different shapes. For example, one or more electrodes maybe curved, flat, straight-edged, rounded, planar, or other shape. Insome embodiments, each of the plurality of electrodes may transmit asignal independently from the other electrodes of the plurality. Inother embodiments, two or more electrodes of the plurality may be synced(e.g., configured to transmit coordinated signals). In some embodiments,in response to a signal that one of either the left stellate ganglion orthe right stellate ganglion is recruited, the recruitment signaltransmitted by one or more electrodes may be adjusted while therecruitment signal transmitted by one or more other electrodes may benot adjusted. For example, in response to a signal that the leftstellate ganglion is recruited (when the right ganglion has not yet beenrecruited), the recruitment signal directed to the left stellateganglion may be ceased or otherwise modified, while the recruitmentsignal directed to the right stellate ganglion may not be adjusted.Similarly, in response to a signal the right stellate ganglion isrecruited (when the left ganglion has not yet been recruited), therecruitment signal directed to the right stellate ganglion may be ceasedor otherwise modified, while the recruitment signal directed to the leftstellate ganglion may not be adjusted.

FIG. 1A illustrates the anatomy of the head and neck and, in particular,the relative locations of the nasoesophageal cavity 110, oroesophagealcavity 115, and esophagus 120. In one or more embodiments an esophagealcatheter 210, including one or more electrodes 220, may be insertedthrough a nasoesophgeal cavity 110 and into the esophagus 120. Althoughnot shown in FIG. 1A, in some embodiments, esophageal catheter 210 maybe inserted through oroesophageal cavity 115 into esophagus 120.Esophageal catheter 210 may be positioned such that one or moreelectrodes 220 are proximate to one or more nerves (e.g., sympatheticganglia).

Referring to FIG. 1B, a system is shown according to one or moreembodiments where esophageal catheter 210 is incorporated with orincludes a feeding tube 230. According to some embodiments, a feedingtube 230 may travel from the exterior of a patient through thenasoesophgeal cavity 110 or an oroesophageal cavity 115 into theesophagus 120. One or more electrodes 220 of esophageal catheter 210 maybe positioned in the esophagus 220 and proximate to one or more nerves(e.g., sympathetic ganglia). A distal end 260 of the feeding tube 230may extend into the stomach 140 allowing for material to be passed fromthe exterior of the patient to the stomach 140 via feeding tube 230without disturbing the placement of the one or more electrodes 220.Esophageal catheter 210 may be placed over an already inserted feedingtube 230, using the feeding tube 230 as a guide for the placement ofesophageal catheter 210. In other embodiments, esophageal catheter 210may be inserted next to and coupled to an already inserted feeding tube230, e.g., as a side tube. In such embodiments, the esophageal catheter210 and feeding tube 230 may occupy non-coaxial spaces within anesophagus 120. In some embodiments, electrodes 220 may be positioned,via a biocompatible adhesive or other suitable anchoring mechanism, onan outer surface of feeding tube 230. In further embodiments, esophagealcatheter 210 may include a thermal probe to measure one or more internaltemperatures.

In one or more embodiments, esophageal catheters 210 are readily appliedto, or inserted into, the patient. The placement or insertion may betemporary, and catheter 210 may be easily removed from the patient at alater time without the need for surgery. In some embodiments, esophagealcatheter may be left in the esophagus 120 of a patient for greater thanor equal to 24 hours, greater than 7 days, greater than 10 days, greaterthan 14 days, greater than 21 days, greater than 28 days, or evengreater than 30 days. For example, esophageal catheter 210 may bewithdrawn once the patient is determined to no longer have an SAH and/oronce the patient is no longer at risk, or is at a significantly reducedrisk, for an SAH-mediated delayed CVS.

FIG. 2A further illustrates the anatomy of the neck and, in particular,the relative locations of esophagus 120, trachea 122, vertebra 124, leftstellate ganglion 314 and right stellate ganglion 312. The cross-sectionshown in FIG. 2A is representative of any axial cross-section taken inthe C4 to T2 region. The sympathetic ganglia includes the left stellateganglion 314 and the right stellate ganglion 312. Further, each of theleft stellate ganglion 314 and the right stellate ganglion 312 may havemore than one branch. In some embodiments, vertebra 124 may be the C5vertebra, the C6 vertebra, or the C7 vertebra.

Referring to FIG. 2B, the same axial cross section of the neck anatomyis taken as FIG. 2A, however FIG. 2B also depicts the placement ofelectrodes 220 of an esophageal catheter 210. As can be seen in FIG. 2B,esophagus 120 is maintained in an enlarged and distended state whileesophageal catheter 210 is inserted therein. One or more electrodes 220may be positioned proximate to the sympathetic ganglia, including, forexample, left stellate ganglion 314 and/or right stellate ganglion 312.In some embodiments, the lumen of esophagus 120 may distend up toapproximately 3 cm (e.g., up to approximately 2 cm) in theanterior-posterior dimension and up to approximately 5 cm (e.g., up toapproximately 3 cm) in a lateral dimension.

FIG. 3A illustrates an exemplary intermediate section of an esophagealcatheter 210 including an inflation lumen 255, inflatable (expandable)member 250, electrodes 220, and feeding tube 230. The inflation member250 runs along a length of the tubular esophageal catheter (e.g.,occupying an intermediate section of the catheter length) andencompasses, encloses, or circumscribes the exterior of feeding tube230, as shown in cross-section FIG. 3B. Inflation lumen 255 may extendproximally from the inflatable member 250 to the exterior of thepatient, where it may be coupled to a controller and/or a fluidproviding device or source. Fluid (e.g., air, saline, water) may betransported from the fluid providing device exterior of the patient tothe inflatable member 250 via the inflation lumen 255. Thetransportation of fluid to the inflatable member 250 may cause theintermediate section of esophageal catheter 210 (e.g., the inflatablemember 250) to expand from a contracted state to an expanded state. Inone example, inflation member 250 may be a compliant or semi-compliantballoon. In other embodiments, an intermediate section may include anactuating member until tensile stress that is operable to expand theintermediate member upon movement and/or adjustment of the actuatingmember.

Electrodes 220 may comprise traditional electrode metals such as, forexample, stainless steel, gold, or an alloy including platinum andiridium. Each electrode may have an exposed surface area greater than orequal to 1.5 mm², such as, for example, greater than or equal to 2 mm²,greater than or equal to 2.5 mm², greater than or equal to 3 mm²,greater than or equal to 4 mm², or greater than or equal to 5 mm².Electrodes 220 may have a surface area such that a recruitment signalmay be transmitted without damage to the electrode 220 or surroundingtissue. Electrodes 220 may be configured to have a surface area suchthat a transmitted charge density does not exceed therapeutic levels.Electrode 220 a is positioned on a surface of the catheter opposite toelectrode 220 c (on an opposing side of longitudinal axis 224), and bothelectrodes 220 a and 220 c may be at the same axial position alonglongitudinal axis 224. Similarly, electrode 220 b is positioned on asurface of the catheter opposite to electrode 220 d (on opposing sidesof longitudinal axis 224), and both electrode 220 b and electrode 220 dmay be positioned at the same axial position along longitudinal axis 224(and longitudinally staggered from electrodes 220 a and 220 c).Electrode 220 a may be longitudinally aligned with electrode 220 c, andelectrode 220 b may be longitudinally aligned with electrode 220 d. Allelectrodes 220 may be independently controlled to transmit differentelectrical signals. In one or more embodiments, electrodes 220 a and 220b are configured to transmit the same electrical signal. In someembodiments, two or more electrodes may be configured to be synced,where one electrode serves as the source of the electrical signaltransmission and a second electrode may be the sink (e.g., the returnelectrode). In other embodiments, electrodes 220 c and 220 d may beconfigured to transmit the same electrical signal. As seen in FIG. 3B,catheter 210 includes a first lateral axis 222 (a major lateral axis),and a second lateral axis 223 (a minor lateral axis, e.g., anantero-posterior axis). First lateral axis 222 and second lateral axis223 are both substantially perpendicular to longitudinal axis 224, andare substantially perpendicular to one another. Inflatable member 250may have a larger dimension in the expanded state along first lateralaxis 222 than along second lateral axis 223. Electrodes 220 may bepositioned on inflatable member 250 on only one side of first lateralaxis 222, while no electrodes 220 are positioned on inflatable member250 on an opposing side of first lateral axis 250. This positioning maybe based on the positions of left stellate ganglion 314 and rightstellate ganglion 312 on only one lateral side of esophagus 120 as shownin FIGS. 2A and 2B. Electrodes 220 may be affixed or otherwise coupledto the exterior (outer surface) of esophageal catheter 210. In someembodiments, electrodes 220 may be embedded into esophageal catheter 210and windows on the catheter may expose electrodes, allowing for aconductive path between electrodes 220 and surrounding tissue, includingthe esophagus in which catheter is inserted. Alternatively, electrodescould be printed onto the surface of the catheter by one of severalknown means (e.g. conductive inks, polymers) as described in U.S. Pat.No. 9,242,088, which is incorporated by reference herein. Further, theelectrodes may be integrated into a flexible printed circuit, which canbe attached to, or integrated into, the catheter. Insulation means knownin the art may be used to ensure that the electrodes, and not anyunwanted electrical elements, are exposed to direct contact with thepatient. Esophageal catheter 210 may include rows of apertures orwindows positioned proximally, medially and distally, such that whenesophageal catheter 210 is inserted into an esophagus, at least onewindow may face, abut, or be positioned in the vicinity of the leftstellate ganglion 314, at least one window may face, abut, or bepositioned in the vicinity of the right stellate ganglion 312, and/or atleast one window may face, abut, or be positioned in the vicinity of thesympathetic ganglia. Electrodes 220 may extend partially around thecircumference of esophageal catheter 210. This electrode configurationmay allow electrodes 220 to target a desired nerve for stimulation whileminimizing application of electrical charge to undesired areas of thepatient's anatomy (e.g., other nerves or the heart). The oral cathetermay include one or more features (anchor, hooks, biocompatible adhesive,or the like) to secure or stabilize the catheter within the patient, andor the electrodes 220 at a specific location. Further, esophagealcatheter 210 may be shaped to conform to the inner wall of the esophagusand position at least one electrode proximate the sympathetic ganglia.In some embodiments, esophageal catheter 210 is shaped to dispose atleast two electrodes proximate to each of the left stellate ganglion andright stellate ganglion.

The dimensions of esophageal catheter 210 may be customized inaccordance with the anatomy of a particular patient (e.g., differentsizes of humans, pigs, chimpanzees, etc.). The catheter may have alength greater than or equal to 20 cm, such as for example, 25 cm, 30cm, 35 cm, 40 cm, 45 cm, or 50 cm. Esophageal catheter 210 may also havean outer diameter less than or equal to 10 mm, such as for example, lessthan or equal to 8 mm, less than or equal to 6 mm, less than or equal to5 mm, or less than or equal to 4 mm.

Esophageal catheter 210 may incorporate markings or other indicators onits exterior to help guide the positioning and orientation of thedevice. The catheter may also include internal indicators (e.g.,radiopaque markers, contrast material such as barium sulfate, echogenicmarkers) visible by x-ray, ultrasound, or other imaging technique toassist with positioning esophageal catheter 210 in the desired location.In one or more embodiments, a radiopaque marker 275 may be placed on oradjacent to an electrode 220, as shown in FIG. 3A. In some embodiments,markers may correspond to positions of electrodes on only one side oflateral axis 222. Esophageal catheter 210 may include any combination ofthe features described herein. Accordingly, the features of the catheterare not limited to any one specific combination shown in theaccompanying drawings.

As previously stated, aspects of one embodiment may be combined withaspects of one or more other embodiments. For example, the descriptionof electrodes 220, their integration into esophageal catheter 210, andtheir placement proximate to sympathetic ganglia (e.g., left stellateganglion 314 and/or right stellate ganglion 312) may be applicable toany esophageal catheter described herein. Referring now to FIGS. 4A-4B,an esophageal catheter 410 may include an intermediate sectioncomprising two or more expandable arms 260 connected by a tether 265,which is slack in the contracted state shown in FIGS. 4A and 4B. In acontracted state, at least the intermediate section of catheter 410 isdisposed within a sheath 270. Each arm 260 may include a joined end 262,a proximal end 268, and at least one electrode 220 positioned betweenthe joined end 262 and the proximal end 268. Each joined end 262 mayconnect to the joined ends 262 of the other arms 260 at the distal endof catheter 410. For example, joined end 262 a of arm 260 a connects tojoined end 262 b of arm 262 b by a weld or other suitable connection, asshown in FIG. 4A. Further, the proximal end 268 of each arm 260 isfurther displaced from the proximal end 268 of the other arms 260 whenin an expanded state as compared to in a contracted state. For example,proximal end 268 a of arm 260 a is farther displaced from proximal end268 b of arm 260 b when the intermediate section of esophageal catheter210 expands to an expanded state, as shown in FIGS. 4A-4B.

Another exemplary intermediate section of esophageal catheter 210 shownin FIGS. 4A-4B is in a contracted state and disposed in a sheath 170.The shape of the catheter may be formed by heat setting the sheath 170,or by adding a shaped stainless steel wire or a shape memory nitinolwire or any other shape memory alloy. A shape-memory alloy may activatea helical shape of esophageal catheter 210 when heated to a temperatureof 30° C. to 45° C., such as, for example, 37° C. When esophagealcatheter 210 is deployed and removed from sheath 170 the proximal ends268 of the intermediate section of the catheter may expand and displacefarther apart, as shown in FIGS. 4C-4D. In other words, catheter 210 maybe biased into the expanded state. As shown in FIG. 4C, the tether 265is stretched taut, limiting the extent to which proximal ends 268 mayradially separate and expand away from one another. This expandedhelical shape may help anchor esophageal catheter 210 to the esophagusand/or to stabilize the catheter during nerve recruitment. The helicalshape may position electrodes 220 at different radial positions withinthe esophagus and relative to target nerves such as for example the leftstellate ganglion and/or right stellate ganglion. In some embodiments,all electrodes of an esophageal catheter 210 may be positioned on oneside of the first lateral axis 222.

Referring now to FIG. 5A, an exemplary intermediate section of anesophageal catheter 210 in a contracted state is shown. FIGS. 5B-5C showthe same intermediate section of esophageal catheter 210 in an expandedstate. The catheter may include an intermediate section comprising twoor more arms 260 on opposing sides of inflatable member 250 and aninflation lumen 255 connected to the inflatable member 250. Each arm 260may include a joined end 262, a proximal end 268, and at least oneelectrode 220 positioned between the joined end 262 and the proximal end268. Each joined end 262 may connect to the joined ends 262 of the otherarms 260. For example, joined end 262 a of arm 260 a connects to joinedend 262 b of arm 262 b, as shown in FIG. 5A. Further, the proximal end268 of each arm 260 is further displaced from the proximal end 268 ofthe other arms 260 when in an expanded state as compared to in acontracted state. For example, proximal end 268 a of arm 260 a isfarther displaced from proximal end 268 b of arm 260 b when theintermediate section of esophageal catheter 210 expands to an expandedstate, as shown in FIGS. 5A-5B.

Inflatable member 250 may be inflated in a substantially similar manneras described above with respect to FIGS. 3A and 3B. The transportationof fluid to the inflatable member 250 may cause the intermediate sectionof esophageal catheter 210 (e.g., the inflatable member 250 and arms260) to expand from a contracted state to an expanded state. In someembodiments, the electrodes 220 may be on only one side of lateral axis222.

FIG. 6 illustrates a block diagram of the various components of system.The system may include a controller 290, which may be part of any of thecontrol units described herein. Each of the components of the system maybe operably coupled to controller 290, and controller 290 may manageoperation of electrodes 220 during nerve recruitment and control thegathering of information by various sensors (510, 520, 530, 540, 550,560) during monitoring of recruitment. It should be understood that thevarious modules described herein may be part of a computing system andare separated in FIG. 6 for explanatory purposes only; it is notnecessary for the modules to be physically separate.

Controller 290 may connect to the esophageal catheter 210 via a leadwire cable 211 and a connector. The lead wire cable may have a lengthgreater than or equal to approximately a meter and the esophagealcatheter may optionally include a feeding tube 230, with an inlet 201for administration of substances including food stuff and nutrients.Controller 290 may connect to one or more sensors. For example, a sensorwhich detects palpebral droop 510, electrodes of an EEG 520, sensorswhich measure pupil diameter 530 (including, e.g., a pupilometer), asensor which detects sclera color change 540, one or more skintemperature sensors 550, or sensors connected to a transcranial Dopplerultrasonogram 560, as described herein. In some embodiments, one or moresensors configured to detect a physiological parameter (e.g., palpebralslump, pupil diameter, sclera color) may include a camera or otherimaging device, one or more photo filers, image recognition/processingsoftware, and/or an algorithm for determining the state of aphysiological parameter based on a captured image. For example, aninfrared camera may be used to monitor skin temperatures over time andone or more image recognition software components or algorithms mayrecognize or detect one or more patterns in the fluctuation of skintemperature. In further embodiments, one or more sensors for detectingskin temperature may include one or more triple-patch electrodes placedon the forehead and/or one or more limbs. In some embodiments, anelectrode, functioning as a sensor, may measure intraocular pressure. Instill other embodiments, one or more electrodes or collection vesiclesmay be placed near or on the skin to measure skin perspiration rateand/or perspiration density.

The one or more sensors may transmit various signals to the operator290, influencing the operator 290 to adjust the electrical signaltransmitted by one or more electrodes 220. For example one or moresensors may transmit a signal to the operator 290 and based on thatsignal, the operator 290 may induce one or more electrodes to adjust theamplitude or frequency of the transmitted electrical signal.

FIG. 7 depicts a flow chart of an exemplary method 600 of treatment,according to the present disclosure. In the discussion below ofexemplary methods and flow charts, reference may be made to thereference numerals detailed in FIGS. 1A-6. In one or more embodiments, amethod of treatment may include positioning a catheter 210 within anesophagus 120 such that at least one electrode 220 of the catheter 210is proximate to at least one sympathetic ganglion (e.g., left stellateganglion 314 and/or right stellate ganglion 312) (step 610). The method600 may further include recruiting the sympathetic ganglia (e.g., leftstellate ganglion 314 and/or right stellate ganglion 312) via anelectrical signal from at least one electrode (step 620). In someembodiments, the method 600 may further include monitoring therecruitment of the sympathetic ganglia (e.g., left stellate ganglion 314and/or right stellate ganglion 312) (step 630). This monitoring mayoptionally be done by one or more of a sensor which detects palpebraldroop 510, electrodes of an EEG 520, sensors which measure pupildiameter 530, a sensor which detects sclera color change 540, one ormore skin temperature sensors 550, or sensors connected to atranscranial Doppler ultrasonogram 560. The method 600 may furtherinclude, based on the monitoring the recruitment of the sympatheticganglia (e.g., left stellate ganglion 314 and/or right stellate ganglion312), adjusting the electrical signal from at least one electrode 220(step 640).

In some embodiments, recruitment of the sympathetic ganglia viahigh-frequency electrical signals using temporary intra-esophagealelectrodes may provide for a simpler, more convenient, and safer methodto transiently and reversibly block the transmission of sympatheticnerve signals than the current standard of care (e.g., percutaneoushypodermic needle injection of anesthesia.

One or more esophageal catheters described herein may have features tomeet unique anatomical and electrical requirements. Intra-esophageallumens, such as, for example, nasogastric feeding tubes or diaphragmaticEMG sensing leads used for neurally adjusted ventilator assist may beinserted in patients and safely left in the patient for days and may beremoved without harm to the patient. Esophageal catheters describedherein may minimize the conduction distance from the stimulation sourceelectrodes to the target sympathetic neurons, maximizing the fieldstrength directed in a lateral and dorsal direction towards targettissue. This may minimize unwanted stimulation of other neuralstructures, such as, for example, the recurrent laryngeal nerves whichare located more medially and anteriorly, and may minimize the risk ofcausing mechanical or electrical damage to the esophageal wall or neuralstructures.

The amplitude of the electrical signal transmitted by one or moreelectrodes of an esophageal catheter (e.g., a recruitment signal) may begraded to select which fibers in a nerve are recruited, based on fibersize and fiber location. Recruitment of a nerve may be suddenly onset(e.g., may occur in less than or equal to 10 ms, such as, less than orequal to 5 ms), may be rapidly released, and/or may persist minutes orhours after recruitment signal is ceased. For example, in someembodiments, a recruitment signal lasting one minute in duration mayrecruit at least one sympathetic ganglion for at least approximately 30minutes.

While principles of the present disclosure are described herein withreference to illustrative embodiments for particular applications, itshould be understood that the disclosure is not limited thereto. Thosehaving ordinary skill in the art and access to the teachings providedherein will recognize additional modifications, applications,embodiments, and substitution of equivalents all fall within the scopeof the embodiments described herein. Accordingly, the invention is notto be considered as limited by the foregoing description.

We claim:
 1. A method of treatment, the method comprising: positioning a catheter within the esophagus, the catheter including at least one electrode, wherein the catheter is positioned so that the at least one electrode is proximate to at least one sympathetic ganglion; and recruiting the at least one sympathetic ganglion via an electrical signal from the at least one electrode.
 2. The method of claim 1, further comprising recruiting at least one of a left stellate ganglion or a right stellate ganglion via an electrical signal from the at least one electrode.
 3. The method of claim 1, wherein the recruiting of the at least one sympathetic ganglion includes blocking transmission of nerve signals along the sympathetic ganglion.
 4. The method of claim 1, wherein the at least one electrode includes a plurality of electrodes, a first electrode of the plurality of electrodes being positioned on a surface opposite a second electrode of the plurality of electrodes, where the first electrode and second electrode are positioned at the same axial level.
 5. The method of claim 4, further comprising recruiting a left stellate ganglion and a right stellate ganglion.
 6. The method of claim 1, wherein the at least one electrode is positioned inferior to the C4 vertebra and superior to the T2 vertebra.
 7. The method of claim 1, wherein the catheter is positioned through an oroesophageal or a nasoesophageal cavity.
 8. The method of claim 1, wherein the electrical signal is pulsed, and has a frequency of 100 Hz to 100 kHz and an amplitude of 10 μA to 20 mA.
 9. The method of claim 1, wherein the at least one electrode includes at least four electrodes.
 10. The method of claim 1, further including monitoring the recruitment of a sympathetic ganglion.
 11. The method of claim 10, wherein monitoring the recruitment of a sympathetic ganglion comprises: observing palpebral droop, performing an electroencephalogram, measuring pupil diameter, observing a color change in a sclera, measuring a skin temperature, performing a transcranial Doppler ultrasonogram, or a combination thereof.
 12. The method of claim 10, further comprising, based on monitoring the recruitment of a sympathetic ganglion, adjusting the electrical signal from at least one electrode.
 13. A system for treatment, the system comprising: an esophageal catheter comprising at least one electrode configured to be positioned within an esophagus proximate to at least one sympathetic ganglion; one or more sensors for sensing a physiologic parameter indicative of a state of the sympathetic ganglion; and a controller in communication with the at least one electrode and the one or more sensors; wherein, upon receiving a first signal from the one or more sensors based on the sensed physiological parameter, the controller induces the at least one electrode to transmit an electrical signal that recruits the sympathetic ganglia.
 14. The system of claim 13, wherein the one or more sensors measure or monitor: pupil dilation, skin temperature, blood flow, electroencephalography, or a combination thereof.
 15. The system of claim 13, wherein upon receiving a second signal from the one or more sensors, the controller induces the at least one electrode to cease transmitting the electrical signal.
 16. The system of claim 13, wherein upon receiving a second signal from the one or more sensors, the controller induces the at least one electrode to adjust one or more of the amplitude or frequency of the transmitted electrical signal.
 17. The system of claim 13, wherein the at least one electrode includes a plurality of electrodes configured to independently transmit electrical signals and a first electrode of the plurality of electrodes is configured to be positioned proximate to a left stellate ganglion and a second electrode of the plurality of electrodes is configured to be positioned proximate to a right stellate ganglion.
 18. The system of claim 17, wherein upon receiving a second signal from one or more sensors, the controller may induce one of the plurality of electrodes to adjust one or more of the amplitude or frequency of the electrical signal.
 19. An esophageal catheter comprising: an intermediate section operable to radially expand from a contracted state to an expanded state; a plurality of electrodes; a feeding tube; wherein at least two of the plurality of electrodes are farther displaced when the intermediate section is in an expanded state.
 20. The esophageal catheter of claim 19, wherein the intermediate section comprises at least two arms.
 21. The esophageal catheter of claim 19, wherein the intermediate section comprises an inflatable member.
 22. The esophageal catheter of claim 19, where the intermediate section includes two or more arms connected by a tether and each arm comprises: a joined end, which connects to the joined end of one or more other arms; a proximal end, which is farther displaced from the proximal end of one or more other arms when the intermediate section is in an expanded state as compared to when the intermediate section is in a contracted state; at least one electrode positioned between the joined end and the proximal end.
 23. The esophageal catheter of claim 22, wherein each arm of the intermediate section comprises a plurality of electrodes.
 24. The esophageal catheter of claim 19, wherein the intermediate section is biased to the expanded state. 